Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy

Molecular Cancer

Review

Seila Lorenzo-Herrero¹  Christian Sordo-Bahamonde¹  Alejandra Martínez-Pérez¹  Segundo Gonzalez¹  Candelaria Aguilar-García¹  Juana M. García-Pedrero²  Juan P. Rodrigo²  Rocío Granda-Díaz² 

[1] Department of Functional Biology, Immunology, Universidad de Oviedo, Oviedo, Spain;Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain;Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain;Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Oviedo, Spain;Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain;Department of Otolaryngology-Head and Neck Surgery, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain;Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain;

关键词: Immunotherapy;    BTLA;    HVEM;    Checkpoint blockade;    T cell;    NK cell;    CD160;    LIGHT;    Icatolimab;    Tifcemalimab;   

DOI  :  10.1186/s12943-023-01845-4

 received in 2023-06-07, accepted in 2023-08-17,  发布年份 2023

来源: Springer

【 摘 要 】

Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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